The steric configuration of the peptide compound of formula (II) has influences on activity. It is particularly preferred that the two asymmetric carbon atoms in the moiety enclosed with a dotted line in formula (II) are both in an S-configuration.
The steric configuration of the above moiety of the peptide compound of formula (II) depends on the starting compound from which the moiety is derived, i.e., an optically active (2S, 3S) -allophenylnorstatin derivative represented by formula (I): ##STR2## wherein R.sup.1 represents an amino group protective group; R.sup.2' represents a hydrogen atom or a lower alkyl group; and R.sup.3' represents a hydrogen atom, a tri(lower alkyl)silyl group or a (lower alkyl)diarylsilyl group.
It is known that (2S,3S)-allophenylnorstatin can be prepared by a process starting with phenylalanine, which comprises oxidizing an alcohol derived from phenylalanine to form an aldehyde, adding hydrogen cyanide to the aldehyde, and inverting the steric configuration of the hydroxyl groups to provide two optically active sites (see J. Med. Chem., Vol. 33, p. 2707, 1990).
However, industrialization of the above process raises problems because of the involvement of an oxidation reaction, a step of using a harmful cyanide, and a step of steric inversion. In addition, since the intermediate aldehyde is very labile and ready to racemize, it has been very difficult to obtain the desired compound at high optical purity. It has therefore been demanded to develop a process for preparing (2S,3S)-allophenylnorstatin derivatives (I) at high optical purity, easily, safely, and in high yield.
Under the circumstances, the inventors of the present invention have conducted extensive investigations and succeeded in preparing an optically active (2S,3S)-allophenylnorstatin derivative easily, safely and in high yield through novel phenylbutyric acid derivative intermediates derived from a 4-phenyl-2-halogeno-3-oxobutyric acid ester as a starting material, and thus completed the present invention.
The process of the present invention is represented by the following reaction scheme: ##STR3## wherein R.sup.1, R.sup.2', and R.sup.3' are as defined above; R.sup.2 represents a lower alkyl group; R.sup.3 represents a hydrogen atom, a tri(lower alkyl)silyl group or a (lower alkyl)diarylsilyl group; and X represents a halogen atom.
That is, the present invention provides a process for preparing an optically active (2S,3S)-allophenylnorstatin derivative represented by formula (I), which comprises asymmetrically hydrogenating a 4-phenyl-2-halogeno-3-oxobutyric acid ester represented by formula (III) in the presence of a ruthenium-phosphine complex to obtain a 4-phenyl-(2S)-halogeno-(3R)-hydroxybutyric acid ester represented by formula (IV), epoxidizing the ester (IV) in the presence of a base to obtain a 4-phenyl-(2S,3R)-epoxybutyric acid ester represented by formula (V), reacting the ester of formula (V) with a tri(lower alkyl)silylazide or a (lower alkyl)diarylsilylazide in the presence of a Lewis acid to obtain a (3S)-azido-4-phenyl-(2S)-trisubstituted silyloxybutyric acid ester represented by formula (VI), hydrogenolyzing the ester of formula (VI) into a (2S,3S)-allophenylnorstatin derivative represented by formula (VII), protecting the amino group of the compound of formula (VII), and, if desired, hydrolyzing the compound of formula (VII) before the amino group protection or the compound of formula (VII) after the amino group protection.